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Begriffe, Krankheiten, Einrichtungen u.v.m., verknüpft mit dem zuständigen Bereich.
Begriffe, Krankheiten, Einrichtungen u.v.m., verknüpft mit dem zuständigen Bereich.
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Im Menüpunkt "Übersicht" sind Einrichtungen unter verschiedenen Gesichtspunkten gruppiert: Kliniken, Abteilungen, Institute, Zentrale Einrichtungen und ähnliches.
Im Menüpunkt "Übersicht" sind Einrichtungen unter verschiedenen Gesichtspunkten gruppiert: Kliniken, Abteilungen, Institute, Zentrale Einrichtungen und ähnliches.
Cancer
Androgen receptor function in prostate cancer
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Androgens are important in several steps of male development
including sexual differentiation, initiation and maintenance of
spermatogenesis or development and maintenance of secondary male
characteristics. In target cells, androgens act via binding to
androgen receptor (AR), a ligand-dependent transcription factor
that directly regulates gene expression and belongs to the nuclear
receptor superfamily. It is well known that in males prostate cancer is associated with abnormal AR structure and function. Adenocarcinoma of the prostate is the second leading cause of cancer deaths among men and becomes the greatest in men after the age of 75 years in Europe and the US. In the initial growing phase prostate tumours grow androgen dependent and respond favorably to androgen suppressing therapy. After a initial androgen dependent growth phase, most prostate tumours enter in a so called androgen independent growth phase and are stimulated by estrogens, progestins, and antiandrogens. Once the tumour has entered the androgen independent growth phase there is no cure and very little treatment options. In general, very little is known about the specific molecular mechanisms controlling the transcriptional activity of the AR in normal prostate and in pathologic situation such as androgen independent prostate tumour growth. In this project, we focused on specific molecular mechanisms involving protein-protein interactions and signaling pathways that control AR transcriptional activity. Importantly, we have identified a novel signaling pathway which is, at least in part, responsible, for androgen independent prostate tumour growth. The identification of this yet undescribed signaling pathway allows us to identify novel therapeutic targets for highly specific pharmaceutical interventions and diagnosis of prostate cancer. |
Characterization of LIM-only coactivators and their regulation by second messenger signaling pathways
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The control of target gene expression by nuclear receptors
requires the recruitment of multiple cofactors. One possible
mechanism to achieve specific gene regulation is the selective
interaction of tissue-restricted cofactors with individual nuclear
receptors. In our previous work (Müller et al. 2000) we
characterized FHL2 (DRAL/Slim3) as the first LIM-only coactivator
of the androgen receptor (AR). FHL2 consists of four and a half LIM domains and exhibits a unique tissue-specific expression pattern. In the adult FHL2 protein is expressed in the myocardium of the heart and in the epithelial cells of the prostate, where it colocalizes with the AR in the nucleus. Interestingly, it is also well expressed in the ovary and bone. FHL2 specifically binds to the AR and selectively increases its transcriptional activity in an agonist- and AF2-dependent manner. Currently, we are interested in the regulation of the transcriptional activity of FHL2. We therefore test the influence of various signal transduction pathways on the transcriptional activity of FHL2 in pathophysiolgical situations, such as heart hypertrophy, dilated cardiomyopathy and metastasis. Furthermore, we functionally analyze FHL2 interacting proteins and study their roles in growth and differentiation. The establishment of mice deficient of FHL2 and transgenic mice overexpressing FHL2 in different tissues allowed us to create suitable animal models and to analyze these question in detail. |
